PRODUCT MONOGRAPH - Sandoz...Lansoprazole, in combination with clarithromycin plus amoxicillin as triple therapy, is indicated for the treatment of patients with H. pylori infection

Sandoz Lansoprazole Page 1 of 82

PRODUCT MONOGRAPH

Pr SANDOZ LANSOPRAZOLE

Lansoprazole Delayed-Release Capsules, USP

15 mg and 30 mg

H+, K+ – ATPase Inhibitor

Sandoz Canada Inc.

110 Rue de Lauzon

Boucherville, QC, Canada

J4B 1E6

Date of Revision:

December 23, 2019

Submission Control No: 234414


Table of Contents

PART I: HEALTH PROFESSIONAL INFORMATION ........................................................................................ 3

SUMMARY PRODUCT INFORMATION .............................................................................................................. 3 INDICATIONS AND CLINICAL USE .................................................................................................................... 3 CONTRAINDICATIONS ........................................................................................................................................ 5 WARNINGS AND PRECAUTIONS ....................................................................................................................... 5 ADVERSE REACTIONS ....................................................................................................................................... 11 DRUG INTERACTIONS ....................................................................................................................................... 21 DOSAGE AND ADMINISTRATION.................................................................................................................... 23 OVERDOSAGE ..................................................................................................................................................... 26 ACTION AND CLINICAL PHARMACOLOGY .................................................................................................. 26 STORAGE AND STABILITY ............................................................................................................................... 31 DOSAGE FORMS, COMPOSITION AND PACKAGING ................................................................................... 31

PART II: SCIENTIFIC INFORMATION .............................................................................................................. 33

PHARMACEUTICAL INFORMATION ............................................................................................................... 33 CLINICAL TRIALS ............................................................................................................................................... 34 DETAILED PHARMACOLOGY .......................................................................................................................... 50 TOXICOLOGY ...................................................................................................................................................... 59 REFERENCES ....................................................................................................................................................... 70

PATIENT MEDICATION INFORMATION ......................................................................................................... 76


Pr SANDOZ LANSOPRAZOLE

Lansoprazole Delayed-Release Capsules, USP

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of

Administration

Dosage Form/

Strength

All Nonmedicinal Ingredients

Oral Delayed-release

capsules/15 mg, 30 mg

D&C yellow No. 10, FD&C blue No. 1 (30 mg

capsules only), FD&C green No. 3 (15 mg

capsules only), FD&C red No. 3, gelatin,

hydroxypropyl cellulose, hypromellose,

macrogol, maize starch, magnesium carbonate,

methacrylic acid-ethyl acrylate copolymer,

polysorbate 80, silica colloidal anhydrous,

sucrose, sugar spheres, talc, titanium dioxide.

INDICATIONS AND CLINICAL USE

NOTE: WHEN USED IN COMBINATION WITH ANTIMICROBIALS FOR THE

ERADICATION OF HELICOBACTER PYLORI (H. pylori), THE PRODUCT

MONOGRAPH FOR THOSE AGENTS SHOULD BE CONSULTED.

Adults

Sandoz Lansoprazole (lansoprazole delayed-release capsules) is indicated in the treatment of

conditions where a reduction of gastric acid secretion is required, such as:

Duodenal ulcer

Gastric ulcer

Reflux esophagitis including patients with Barrett's esophagus, and patients poorly responsive to an adequate course of therapy with histamine H2-receptor antagonists.

Healing of non-steroidal anti-inflammatory drug (NSAID)-associated gastric ulcer; treatment of NSAID-associated gastric ulcer in patients who continue NSAID use

(controlled studies did not extend beyond 8 weeks)

Reduction of risk of NSAID-associated gastric ulcers in patients with a history of gastric ulcers who require to continue taking a NSAID (a controlled study did not extend beyond

12 weeks)

Symptomatic Gastroesophageal Reflux Disease (GERD); treatment of heartburn and other symptoms associated with GERD.

Pathological hypersecretory conditions including Zollinger-Ellison Syndrome (see DOSAGE AND ADMINISTRATION).

Eradication of Helicobacter pylori (H. pylori)


Triple Therapy: Sandoz Lansoprazole/Clarithromycin/Amoxicillin Lansoprazole, in combination with clarithromycin plus amoxicillin as triple therapy, is indicated

for the treatment of patients with H. pylori infection and active duodenal ulcer disease.

Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence (see

CLINICAL TRIALS and DOSAGE AND ADMINISTRATION).

(FOR ADDITIONAL INFORMATION ON TRIPLE THERAPY FOR THE

TREATMENT OF H. PYLORI INFECTION AND ACTIVE DUODENAL ULCER

RECURRENCE, REFER TO THE HP-PAC PRODUCT MONOGRAPH.)

In patients with a recent history of duodenal ulcers who are H. pylori positive, eradication

therapy may reduce the rate of recurrence of duodenal ulcers. The optimal timing for eradication

therapy for such patients remains to be determined.

In patients who fail a therapy combination containing clarithromycin, susceptibility testing

should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not

possible, an alternative therapy combination is recommended.

Resistance to amoxicillin has not been demonstrated in clinical studies with lansoprazole

capsules and amoxicillin.

Table 1 summarizes the eradication rates for the H. pylori Triple Therapy treatment regimens.

Table 1. Eradication Rates for the H. pylori Triple Therapy Treatment Treatment Regimen Days/ Study

No.

Evaluable (Per

Protocol)*

% (n/N)

ITT (all

data)†

% (n/N)

ITT (Worst

Case)‡

% (n/N)

Lansoprazole 30 mg capsules/

clarithromycin 500 mg/

amoxicillin 1000 mg (all twice

daily)

14/ M93-131 92 (44/48) 94 (47/50) 86 (47/55)

14/ M95-392 86 (57/66) 87 (58/67) 83 (58/70)




daily)

10/ M95-399

84 (103/123)

86 (110/128)

81 (110/135)




daily)

7/ GB 94/110

90 (103/114)

90 (104/116)

86 (104/121)

Definitions: ITT = intent-to-treat patients

* Based on evaluable patients with confirmed duodenal ulcer and/or gastritis and H. pylori infection at

baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest®, histology and/or culture. Patients

were included in the analysis if they completed the study. Additionally, if patients dropped out of the study

due to an adverse event related to the study drug, they were included in the analysis as failures of therapy.

† Patients were included in the analysis if they had documented H. pylori infection at baseline as defined

above and had a confirmed duodenal ulcer.

‡ “Worst case” included patients with no available data as failures.

Patients were included in the analysis if they had documented duodenal ulcer (active) and H. pylori infection


at baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest®, histology and/or culture.

Pediatrics (6 to 17 years of age)

Pediatric GERD (erosive and non-erosive esophagitis)

Sandoz Lansoprazole is indicated for treatment of erosive and non-erosive GERD in children,

aged 6 to 17 years. The clinical trial treatment period did not extend beyond 12 weeks.

CONTRAINDICATIONS

Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the DOSAGE FORMS,

COMPOSITION AND PACKAGING section of the Product Monograph.

Amoxicillin is contraindicated in patients with a known hypersensitivity to any penicillin (Please refer to the Amoxicillin Product Monograph before prescribing).

Clarithromycin is contraindicated in patients with known hypersensitivity to

clarithromycin, erythromycin or other macrolide antibacterial agents. Clarithromycin is

also contraindicated in patients receiving concurrent therapy with astemizole, terfenadine,

cisapride or pimozide (please refer to the Clarithromycin tablets Product Monograph

before prescribing).

Co-administration with rilpivirine is contraindicated. See DRUG INTERACTIONS, Table 11.

WARNINGS AND PRECAUTIONS

General

Gastric Malignancy

Symptomatic response to therapy with lansoprazole delayed-release capsules does not preclude

the presence of gastric malignancy.

Pseudomembranous Colitis Pseudomembranous colitis has been reported with nearly all antibacterial agents, including

clarithromycin and amoxicillin, and may range in severity from mild to life threatening.

Serious Warnings and Precautions

If taking lansoprazole in combination with clarithromycin, note that clarithromycin

should not be used in pregnancy except where no alternative therapy is appropriate,

particularly during the first 3 months of pregnancy. If pregnancy occurs while taking

the drug, the patient should be apprised of the potential hazard to the fetus.

Clarithromycin has demonstrated adverse effects on pregnancy outcome and/or

embryo-fetal development in monkeys, mice, rats and rabbits at doses that produced

plasma levels 2 to 17 times the serum levels obtained in humans treated at the maximum

recommended doses (see WARNINGS AND PRECAUTIONS section in the

Clarithromycin Product Monograph).


Therefore, it is important to consider this diagnosis in patients who present with diarrhea

subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit

overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a

primary cause of "antibiotic-associated colitis".

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures

should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation

of the drug alone. In moderate to severe cases, consideration should be given to management

with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug

effective against Clostridium difficile colitis.

Clostridium Difficile-Associated Diarrhea

Decreased gastric acidity due to any means, including proton pump inhibitors (PPIs), increases

gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton

pump inhibitors can lead to an increased risk of gastrointestinal infections such as Salmonella,

Campylobacter and Clostridium difficile.

An increased risk for Clostridium difficile infection (CDI) and Clostridium difficile-associated

diarrhea (CDAD) has been observed in association with PPI use in several observational studies.

CDI/CDAD should be considered in the differential diagnosis for diarrhea that does not improve.

Additional risk factors for CDI and CDAD include recent hospitalization, the use of antibiotics,

old age and the presence of co-morbidities.

Patients should be prescribed PPIs at the lowest dose and for the shortest duration required for

the condition being treated and be reassessed to ascertain whether continued PPI therapy remains

beneficial.

Concomitant Use with Methotrexate

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may

elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to

methotrexate toxicities. A temporary withdrawal of the PPI may be considered in some patients

receiving treatments with high dose methotrexate (see DRUG INTERACTIONS).

H. pylori Eradication and Compliance To avoid failure of the eradication treatment with a potential for developing antimicrobial

resistance and a risk of failure with subsequent therapy, patients should be instructed to follow

closely the prescribed regimen.

For the eradication of H. pylori, amoxicillin and clarithromycin should not be administered to

patients with renal impairment since the appropriate dosage in this patient population has not yet

been established.


Bone Fracture

Several published observational studies suggest that PPI therapy may be associated with an

increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture

was increased in patients who received high-dose, defined as multiple daily doses, and long-term

PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI

therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related

fractures should be managed according to established treatment guidelines (see DOSAGE AND

ADMINISTRATION and ADVERSE REACTIONS).

Carcinogenesis and Mutagenesis

Safety concerns of long-term treatment relate to hypergastrinemia, possible enterochromaffin-

like (ECL) effect and carcinoid formation. ECL cell hyperplasia and gastric carcinoid tumours

were observed in four animal studies. See TOXICOLOGY, Mutagenicity and Carcinogenesis for

further details.

Analysis of gastric biopsy specimens from patients after short-term treatment of proton pump

inhibitors have not detected ECL cell effects similar to those seen in animal studies. Longer term

studies in humans revealed a slight increase in the mean ECL-cell density, although there was no

microscopic evidence of cell hyperplasia. Similar results were seen in the maintenance treatment

studies, where patients received up to 15 months of lansoprazole therapy. Serum gastrin values

increased significantly from their baseline values but reached a plateau after 2 months of therapy.

By 1 month post-treatment, fasting serum gastrin values returned to lansoprazole therapy

baseline. Moreover, results from gastric biopsies from short-term, long-term and maintenance

treatment studies indicate that there are no clinically meaningful effects on gastric mucosa

morphology among lansoprazole-treated patients. For further details, see information under

DETAILED PHARMACOLOGY and TOXICOLOGY.

Drug Interactions with Antiretroviral Drugs

PPIs have been reported to interact with some antiretroviral drugs. The clinical importance and

the mechanisms behind these interactions are not always known. A change in gastric pH may

change the absorption of the antiretroviral drug. Other possible mechanisms are via CYP 2Cl9.

Rilpivirine

Co-administration is contraindicated due to significant decrease in rilpivirine exposure and loss

of therapeutic effect (see CONTRAINDICATIONS).

Atazanavir and Nelfinavir

Co-administration with atazanavir or nelfinavir is not recommended due to decreased atazanavir,

nelfinavir exposure. (see the Atazanavir and Nelfinavir Product Monographs).

If the combination of lansoprazole with atazanavir is judged unavoidable, close clinical clinical

monitoring is recommended in combination with the use of 400 mg atazanavir/100 mg ritonavir

dose; the dose of lansoprazole should not exceed an equivalent dose of omeprazole of 20 mg

daily. (see Atazanavir Product Monograph)."


Saquinavir

If lansoprazole is co-administered with saquinavir/ritonavir, caution and monitoring for potential

saquinavir toxicities, including gastrointestinal symptoms, increased triglycerides, deep vein

thrombosis and QT prolongation, are recommended. Dose reduction of saquinavir should be

considered from the safety perspective for individual patients. (see Saquinavir Product

Monograph).

Endocrine and Metabolism

Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated

with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events

include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia

required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as

digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may

consider monitoring magnesium levels prior to initiation of PPI treatment and periodically (see

ADVERSE REACTIONS).

The chronic use of PPIs may lead to hypomagnesemia. Moreover, hypokalemia and

hypocalcemia have been reported in the literature as accompanying electrolyte disorders.

Cyanocobalamin (Vitamin B12) Deficiency The prolonged use of proton pump inhibitors may impair the absorption of protein-bound

Vitamin B12 and may contribute to the development of cyanocobalamin (Vitamin B12)

deficiency.

Interference with Laboratory Tests

During treatment with antisecretory drugs, chromogranin A (CgA) increases due to decreased

gastric acidity. Increased CgA levels may interfere with investigations for neuroendocrine

tumours. To avoid this interference, lansoprazole delayed-release capsules treatment should be

stopped 14 days before CgA measurements (see DRUG INTERACTIONS).

Gastrointestinal When gastric ulcer is suspected, the possibility of malignancy should be excluded before therapy

with lansoprazole delayed-release capsules is instituted as treatment with this drug may alleviate

symptoms and delay diagnosis.

Long-term use of lansoprazole is associated with an increased risk of fundic gland polyps,

especially beyond one year (see ADVERSE REACTIONS, Post-Market Adverse Drug

Reactions). Most fundic gland polyps are asymptomatic. Use the lowest dose and shortest

duration of PPI therapy appropriate to the condition being treated.

Genitourinary

In the 24-month toxicology study in rats, after 18 months of treatment, Leydig cell hyperplasia

increased above the concurrent and historical control level at dosages of 15 mg/kg/day or higher.


Testicular interstitial cell adenoma also occurred in 1 of 30 rats treated with 50 mg/kg/day

(13 times the recommended human dose based on body surface area) in a 1-year toxicity study.

These changes are associated with endocrine alterations which have not been, to date, observed

in humans. For further details, see information under DETAILED PHARMACOLOGY and

TOXICOLOGY.

Hepatic/Biliary/Pancreatic

Use in Patients with Hepatic Impairment

It is recommended that the initial dosing regimen need not be altered for patients with mild or

moderate liver disease, but for patients with moderate impairment, doses higher than 30 mg per

day should not be administered unless there are compelling clinical indications. Dose reduction

in patients with severe hepatic disease should be considered.

Immune Allergic reactions (including anaphylaxis) have been reported in patients receiving

clarithromycin orally.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in

patients on penicillin therapy. These reactions are more apt to occur in individuals with a history

of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

There have been well documented reports of individuals with a history of penicillin

hypersensitivity reactions who have experienced severe hypersensitivity reactions when treated

with a cephalosporin. Before initiating therapy with any penicillin, careful inquiry should be

made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other

allergens. If an allergic reaction occurs, amoxicillin should be discontinued and the appropriate

therapy instituted.

Serious anaphylactic reactions require immediate emergency treatment with epinephrine,

oxygen, corticosteroids, and airway management, including intubation, as indicated.

Subacute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus (SCLE) has been reported with the use of PPIs. If

lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the

patient should seek medical help promptly and the health care professional should consider

stopping lansoprazole delayed-release capsules. The occurrence of SCLE with previous PPI

treatment may increase the risk of SCLE with other PPIs (see ADVERSE REACTIONS,

PostMarket Adverse Drug Reactions).

Ophthalmologic

Retinal atrophy

In animal studies, retinal atrophy was observed in rats dosed orally for 2 years with lansoprazole

at doses of 15 mg/kg/day and above. These changes in rats are believed to be associated with the

effects of taurine imbalance and phototoxicity in a susceptible animal model.


Clinical data available from long-term lansoprazole delayed-release capsules studies are not

suggestive of any drug-induced eye toxicity in humans. In humans, there are presently no

concerns for ocular safety with short-term lansoprazole treatment and the risks associated with

long-term use for nearly 5 years appear to be negligible.

The finding of drug-induced retinal atrophy in the albino rat is considered to be species-specific

with little relevance for humans. For further details, see information under DETAILED

PHARMACOLOGY and TOXICOLOGY.

Renal

No dosage adjustment of lansoprazole is necessary in patients with renal impairment. See

DOSAGE AND ADMINISTRATION and ACTION AND CLINICAL PHARMACOLOGY.



been established.

Sensitivity/Resistance

Antibiotic Resistance in Relation to H. pylori Eradication Three patients [3/82 (3.7%)] who had isolates susceptible to clarithromycin pretreatment and

were treated with the triple therapy regimen remained H. pylori positive post-treatment. None of

the isolates from these 3 patients had susceptibility results available after treatment with triple

therapy; therefore, it is unknown whether or not these patients developed resistance to

clarithromycin. Sixteen percent of the patients treated with the dual therapy regimen developed

clarithromycin resistance post-treatment. Therefore, development of clarithromycin resistance

should be considered as a possible risk.

Use in Women

Over 4000 women were treated with lansoprazole. Ulcer healing rates in females were similar to

those in males. The incidence rates of adverse events are also similar to those seen in males.

Special Populations

Pregnant Women: Reproductive studies conducted in pregnant rats at oral doses up to

150 mg/kg/day (40 times the recommended human dose based on body surface area), and in

rabbits at oral doses up to 30 mg/kg/day (16 times the recommended human dose based on body

surface area), revealed no lansoprazole-related impairment of fertility, fetal malformations or

developmental toxicity to fetuses or suckling neonates. Lansoprazole is not considered to be

teratogenic.

Maternal toxicity and a significant increase in fetal mortality were observed in the rabbit study at

doses above 10 mg/kg/day. In rats, maternal toxicity and a slight reduction in litter survival and

weights were noted at doses above 100 mg/kg/day. See TOXICOLOGY, Reproduction and

Teratology.


There are no adequate or well-controlled studies in pregnant women. Therefore, lansoprazole

should be used with caution during pregnancy only if the potential benefit justifies the potential

risk to the fetus.

If taking lansoprazole in combination with clarithromycin, refer to complete Product Monograph

for clarithromycin before using in pregnant women.

Nursing Women: Lansoprazole or its metabolites are excreted in the milk of rats. It is not

known whether lansoprazole is excreted in human milk. As many drugs are excreted in human

milk, lansoprazole should not be given to nursing mothers unless its use is considered essential.

In this case nursing should be avoided.

Pediatrics (6 to 17 years of age): Safety and effectiveness have been established in pediatric

patients 6 to 17 years of age for short-term treatment of up to 12 weeks of symptomatic GERD

and erosive esophagitis. Use of lansoprazole in this population is supported by evidence of

adequate and well controlled studies of lansoprazole in adults with additional clinical,

pharmacokinetic, pharmacodynamic, and safety studies performed in pediatric patients. The

adverse events (AEs) profile in pediatric patients is similar to that of adults. There were no

adverse events reported in U.S. clinical studies that were not previously observed in adults. Dose

safety and effectiveness have not been established in patients 71 years of age) may already be at high risk for osteoporosis-related

fractures. If the use of PPIs is required, they should be managed carefully according to

established treatment guidelines (see DOSAGE AND ADMINISTRATION and ADVERSE

REACTIONS).

Ulcer healing rates in elderly patients are similar to those in younger age groups. The incidence

rates of adverse events and laboratory test abnormalities are also similar to those seen in other

age groups. The initial dosing regimen need not be altered for elderly patients, but subsequent

doses higher than 30 mg per day should not be administered unless additional gastric acid

suppression is necessary.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

Since 1991, lansoprazole has been approved in over 100 countries around the world, and about

250 million patients have been treated. Worldwide, over 10,000 patients have been treated with

lansoprazole during Phase II-III short-term and long-term clinical trials involving various

dosages and duration of treatment. In general, lansoprazole treatment has been well tolerated.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates

observed in the clinical trials may not reflect the rates observed in practice and should not be


compared to the rates in the clinical trials of another drug. Adverse drug reaction information

from clinical trials is useful for identifying drug-related adverse events and for approximating

rates.

Lansoprazole delayed-release capsules

Short-Term Studies

The following adverse events were reported to have a possible or probable relationship to drug as

described by the treating physician in 1% or more of lansoprazole delayed-release capsules-

treated patients who participated in placebo- and positive-controlled trials (Table 2 and Table 3,

respectively). Numbers in parentheses indicate the percentage of the adverse events reported.

Table 2. Incidence of Possibly or Probably Treatment-Related Adverse Events in Short-

Term, Placebo-Controlled Studies in Takeda* Safety Database Body System/ Adverse Event† Lansoprazole‡

(N=817)

N (%)

Placebo

(N=254)

N (%)

Body as a Whole Headache 63 (7.7) 31 (12.2) Abdominal Pain 19 (2.3) 3 (1.2) Digestive System Diarrhea 29 (3.5) 6 (2.4) Nausea 9 (1.1) 5 (2.0) Vomiting 7 (0.9) 3 (1.2) Liver Function Tests Abnormal 2 (0.2) 3 (1.2) Nervous System Dizziness 8 (1.0) 2 (0.8)

* Takeda Pharmaceuticals America, Inc. † Events reported by at least 1% of patients on either treatment are included. ‡ Doses 15 mg, 30 mg and 60 mg once daily for 4 to 8 weeks.

In the Takeda Safety Database, all short-term, Phase II/III studies, one or more treatment-

emergent adverse events were reported by 715/1359 (52.6%) lansoprazole-treated patients; of

those considered to be possibly or probably treatment-related adverse events, one or more were

reported by 276/1359 (20.3%) lansoprazole-treated patients. In all short-term, Phase II/III

studies, one or more treatment-emergent adverse events were reported by 150/254 (59.1%)

placebo-treated patients; of those considered to be possibly or probably treatment-related adverse

events, one or more were reported by 56/254 (22.0%).

The most frequent adverse events reported in the European short-term studies were diarrhea

(3.3%), laboratory test abnormal (2.3%), headache (1.5%), constipation (1.2%), asthenia (1.1%),

dizziness (1.1%), and abdominal pain (1.0%). The most frequent adverse events reported in the

Asian short-term studies were unspecified laboratory test abnormalities (7.3%), eosinophilia

(1.0%), and increased SGPT (1.0%).


Table 3. Incidence of Possibly or Probably Treatment-Related Adverse Events in Short-

Term, Positive-Controlled Studies in Takeda Safety Database Body System/ Adverse Event*

Lansoprazole†

(N=647)

N (%)

Ranitidine

(N=393)

N (%) Body as a Whole Headache 26 (4.0) 14 (3.6) Abdominal Pain 8 (1.2) 3 (0.8) Digestive System Diarrhea 27 (4.2) 8 (2.0) Nausea 7 (1.1) 4 (1.0) Nervous System Dizziness 8 (1.2) 3 (0.8) Skin and Appendages Rash 7 (1.1) 1 (0.3)

* Events reported by at least 1% of patients on either treatment are included. † Doses 15 mg, 30 mg and 60 mg once daily for 4 to 8 weeks.

NSAID-Associated Gastric Ulcer Studies

The following tables summarize the most frequently reported treatment-emergent adverse events

in the two (2) Healing studies and the Reduction of Risk study (Table 4 and Table 5,

respectively).

Table 4. Most Frequently Reported* Treatment-Emergent Adverse Events by Treatment

Group and Dose in the Principal Healing of NSAID-Associated Gastric Ulcer Studies† Body System/

COSTART Term

Ranitidine

150 mg twice daily

(N=235)

(%) (n)

Lansoprazole

15 mg once daily

(N=235)

(%) (n)

Lansoprazole

30 mg once daily

(N=231)

(%) (n)

Total Patients

Any Event 47% (110) 43% (102) 52% (120)

Body as a Whole

Abdominal Pain 7% (17) 3% (7) 5% (11)

Digestive System

Diarrhea 8% (19) 11% (25) 9% (21)

Respiratory System

Pharyngitis 7% (16) 6% (13) 7% (17)

* Reported by ≥ 5% of patients in any treatment group † Treatment Duration: 8 weeks


Table 5. Most Frequently Reported* Treatment-Emergent Adverse Events by Treatment

Group and Dose in the Principal Reduction of Risk of NSAID-Associated Gastric Ulcer

Studies† Body System/

COSTART Term

Placebo

(N = 133)

% (n)

Misoprostol

200 mcg four times daily

(N = 134)

% (n)

Lansoprazole

15 mg once daily

(N = 136)

% (n)

Lansoprazole

30 mg once daily

(N = 132)

% (n)

Body as a Whole

Abdominal Pain 7% (9) 10% (14) 7% (9) 6% (8)

Digestive System

Diarrhea 7% (9) 25% (33)‡,§,¶ 10% (14) 13% (17)

Nausea 5% (6) 6% (8) 1% (2) 5% (6)

Respiratory System

Pharyngitis 3% (4) 9% (12) 7% (10) 9% (12)‡

Sinusitis 2% (3) 2% (3) 5% (7) 6% (8)

Urogenital System

Urinary Tract Infection 2% (2) 7% (9)¶ 4% (6) 1% (1)

* Reported by ≥ 5% of patients in any treatment group † Treatment Duration: 12 weeks

‡ Statistically significant difference versus placebo (p ≤ 0.05)

§ Statistically significant difference versus lansoprazole 15 mg once daily (p ≤ 0.05)

¶ Statistically significant difference versus lansoprazole 30 mg once daily (p ≤ 0.05)

Gastroesophageal Reflux Disease (GERD) Studies

U.S. Placebo-Controlled Studies

All adverse events considered possibly/probably treatment-related with an incidence of at least

5% in any treatment group are displayed by COSTART body system and term and by treatment

group in Table 6.

Table 6. Adverse Events Possibly/Probably Related to Treatment, Reported by ≥ 5% of

Patients in the U.S. Placebo-Controlled Non-Erosive GERD Studies Body System/ COSTART term Placebo Lansoprazole*

N=71

% (n)

N=249

% (n)

Total patients Any event 16.9 (12) 28.5 (71)† Body as a Whole Abdominal Pain 1.4 (1) 6.0 (15) Headache 7.0 (5) 7.6 (19) Digestive System Diarrhea 2.8 (2) 5.2 (13)

† Statistically significantly different versus placebo at p = 0.05 level.

* Doses 15 mg and 30 mg once daily for 8 weeks.

The most commonly reported (incidence ≥ 5% in any treatment group) treatment-emergent

adverse events for lansoprazole patients were headache (14.9%), pharyngitis (9.6%), abdominal

pain (8.8%), diarrhea (7.6%) and rhinitis (6.4%) and for placebo patients were headache (9.9%)

and pharyngitis (9.9%). There were no clinically or statistically significant differences between

lansoprazole and placebo when evaluated for treatment-emergent adverse events.


U.S. Positive-Controlled Studies

All possibly/probably treatment-related adverse events with an incidence of at least 5% in either

treatment are displayed by body system, COSTART term, and treatment in Table 7.

Table 7. Most Frequently* Reported Possibly/Probably Treatment-Related Adverse Events

by Treatment in the Positive-Controlled Non-Erosive GERD Studies Body System/COSTART term Ranitidine

150 mg twice daily

(N=283)

% (n)

Lansoprazole †

15 and 30 mg once daily

(N=572)

% (n)

Total Patients Any event

17 (49)

16 (91) Body as a Whole Abdominal Pain 2 (5) 5 (29) ‡ Digestive System Diarrhea 6 (18) 4 (23)

* Reported by ≥ 5% of patients in any treatment. † Statistically significantly different versus ranitidine at p = 0.05 level. ‡ Doses 15 mg and 30 mg once daily for 8 weeks.

The most frequently reported (≥ 5% of patients in any treatment) treatment-emergent adverse

events for lansoprazole-treated patients were abdominal pain (9%), diarrhea (7%), and headache

(6%) and for ranitidine-treated patients were diarrhea (9%), abdominal pain (7%), and headache

(7%). There were no clinically or statistically significant differences between lansoprazole- and

ranitidine-treated patients in the percentage of patients reporting specific treatment-emergent

adverse events.

Maintenance Studies

U.S. Studies

Treatment-emergent adverse events with an incidence of at least 2% in any treatment group of

the maintenance treatment studies occurring from the start of maintenance treatment to the first

recurrence of disease are displayed by body system and COSTART term, and by treatment group

in Table 8.

There were no frequently reported (≥ 2.0%, incidence) severe adverse events in the treatment-

emergent or the possibly/probably treatment-related event categories with onset at any point

from the start of maintenance treatment to the time of first recurrence of disease.


Table 8. Treatment-Emergent Adverse Events Reported by ≥ 2% of the Placebo and

Lansoprazole Patients to the Time of First Recurrence of Disease* in the Maintenance

Treatment Studies

Mean Exposure (Days)

Placebo Lansoprazole

Cumulative Cumulative

N=236 (105.4) N=386 (267.5)

Body System/COSTART term % (n) % (n)

Total patients

Any event 39.4 (93) 70.5 (272)

Body as a Whole

Abdominal pain 3.0 (7) 5.2 (20)

Accidental injury 2.1 (5) 5.4 (21)

Back pain 4.2 (10) 3.1 (12)

Chest pain 0.8 (2) 2.3 (9)

Flu syndrome 3.8 (9) 7.3 (28)

Headache 6.4 (15) 11.4 (44)

Infection 1.3 (3) 2.1 (8)

Pain 0.8 (2) 2.6 (10)

Digestive System

Diarrhea 5.5 (13) 9.8 (38)

Gastrointestinal anomaly (polyp) 0.8 (2) 4.4 (17)

Nausea 1.3 (3) 2.8 (11)

Tooth disorder 0.4 (1) 2.1 (8)

Vomiting 0.4 (1) 3.4 (13)

Musculoskeletal System

Arthralgia 1.3 (3) 4.4 (17)

Myalgia 1.3 (3) 2.1 (8)

Nervous System

Dizziness 0.4 (1) 2.8 (11)

Respiratory System

Bronchitis 1.3 (3) 3.1 (12)

Cough increased 0 2.3 (9)

Pharyngitis 9.3 (22) 17.1 (66)

Rhinitis 1.3 (3) 5.7 (22)

Sinusitis 2.5 (6) 6.5 (25)

Skin and Appendages

Rash 3.0 (7) 4.7 (18)

Urogenital System

Urinary tract infection 2.5 (6) 4.1 (16)

* Until time of first recurrence, withdrawal or end of maintenance treatment

European Studies

The adverse events reported by at least 2% of patients in any treatment group are displayed by

COSTART body system and term and by treatment group for controlled long-term European

Studies in Table 9.


Table 9. Treatment-Emergent Adverse Events Reported by ≥ 2% of Patients Treated with

Histamine H2-Receptor Antagonists or Lansoprazole in Long-Term, Phase II/III

Histamine H2-Receptor Antagonist Controlled European Studies Body System/COSTART term Lansoprazole

(N=263)

% (n)

Histamine H2-Receptor Antagonists

(N=161)

% (n)

Total patients

Any event 49.8 (131) 46.6 (75)

Body as a Whole

Abdominal pain 3.0 (8) 3.7 (6)

Back pain 2.3 (6) 0.6 (1)

Accidental injury 1.5 (4) 2.5 (4)

Infection 1.1 (3) 3.1 (5)

Cardiovascular System

Hypertension 1.9 (5) 2.5 (4)

Digestive System

Diarrhea 9.1 (24) 4.3 (7)

Gastritis 5.3 (14) 1.2 (2)

Constipation 2.7 (7) 2.5 (4)

Vomiting 1.9 (5) 3.1 (5)

Dyspepsia 1.1 (3) 3.1 (5)

Musculoskeletal System

Arthralgia 1.9 (5) 2.5 (4)

Nervous System

Dizziness 1.9 (5) 2.5 (4)

Respiratory System

Respiratory Disorder 2.3 (6) 3.1 (5)

Cough increased 1.1 (3) 2.5 (4)

The adverse events reported by at least 1% of patients receiving lead-in open-label lansoprazole

treatment in long-term European Studies are diarrhea (5.7%), esophagitis (2.5%), abdominal pain

(2.1%), gastritis (2.1%), flatulence (1.3%), headache (1.1%), constipation (1.0%), and nausea

(1.0%). The incidence of adverse events reported in the lead-in open-label period of the

European studies was similar to that seen in controlled studies, however, the overall incidence

was lower for the lead-in open- label studies than for the Histamine H2-Receptor Antagonist

controlled studies (27.5% versus 49.8%, respectively).

Pediatrics

The adverse event profile in pediatric patients resembled that of adults taking lansoprazole. The

most frequently reported (2 or more patients) treatment-related adverse events in patients 1 to

11 years of age (N=66) were constipation (5%) and headache (3%). There were no adverse

events reported in this U.S. clinical study that were not previously observed in adults.

The most frequently reported (at least 3%) treatment-related adverse events in patients 12 to

17 years of age (N=87) were headache (7%), abdominal pain (5%), nausea (3%) and dizziness

(3%). Treatment-related dizziness, reported as occurring in


In another study, an 8½-year-old female experienced moderate hot flashes and arterial

hypertension after receiving lansoprazole 17.7 mg/m2 for 5 days. However, blood pressure values

were not recorded. The investigator considered the event possibly related to study drug. Study

drug was discontinued and the symptoms resolved. This child experienced the same side effects

at a later date when treated with ranitidine.

Less Common Clinical Trial Adverse Drug Reactions (


Respiratory System: Asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis,

hiccup, laryngeal neoplasia, pleural disorder, pneumonia, stridor, upper respiratory

inflammation/infection;

Skin and Appendages: Acne, alopecia, contact dermatitis, dry skin, fixed eruption, hair

disorder, maculopapular rash, nail disorder, pruritus, rash, skin carcinoma, skin disorder,

sweating, urticaria;

Special Senses: Abnormal vision, blurred vision, conjunctivitis, deafness, dry eyes, ear disorder,

eye pain, ophthalmologic disorders, otitis media, parosmia, photophobia, retinal degeneration,

taste loss, taste perversion, tinnitus, visual field defect;

Urogenital System: Abnormal menses, breast enlargement, breast tenderness, dysmenorrhea,

dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea, menorrhagia,

menstrual disorder, penis disorder, polyuria, testis disorder, urethral pain, urinary frequency,

urination impaired, urinary urgency, vaginitis.

* The majority of hematologic cases received were foreign-sourced and their relationship to lansoprazole was

unclear.

Combination Therapy with Clarithromycin and Amoxicillin In clinical trials using combination therapy with lansoprazole delayed-release capsules plus

clarithromycin and amoxicillin, and lansoprazole delayed-release capsules plus amoxicillin, no

adverse reactions related to these drug combinations were observed. Adverse reactions that have

occurred have been limited to those that have been previously reported with lansoprazole

delayed-release capsules, clarithromycin, or amoxicillin.

For more information on adverse reactions with clarithromycin or amoxicillin, refer to their

respective Product Monographs, under the ADVERSE REACTIONS section.

Triple Therapy: lansoprazole/clarithromycin/amoxicillin The most frequently reported adverse events for patients who received triple therapy were

diarrhea (7%), headache (6%), and taste perversion (5%). Patients in the 7-day triple therapy

regimen reported fewer adverse events than those in the 10 and/or 14-day triple therapy

regimens. There were no statistically significant differences in the frequency of reported adverse

events between the 10 and 14-day triple therapy regimens.

Abnormal Hematologic and Clinical Chemistry Findings

In addition, the following changes in laboratory parameters were reported as adverse events.

Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased

creatinine, increased alkaline phosphatase, increased gamma globulins, increased GGTP,

increased/decreased/abnormal white blood cells (WBC), abnormal AG ratio, abnormal red blood

cells (RBC), bilirubinemia, eosinophilia, hyperlipemia, increased/decreased electrolytes,

increased/decreased cholesterol, increased glucocorticoids, increased lactate dehydrogenase

(LDH), increased/decreased/abnormal platelets, and increased gastrin levels. Urine abnormalities

such as albuminuria, glycosuria, and hematuria were also reported. Additional isolated laboratory

abnormalities were reported.


In the placebo controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4%

(4/978) and 0.4% (11/2677) patients, who received placebo and lansoprazole, respectively, had

enzyme elevations > 3 x upper limit of normal range at the final treatment visit. None of these

lansoprazole-treated patients reported jaundice at any time during the study.

For more information on laboratory value changes with clarithromycin or amoxicillin, refer to

their respective Product Monographs, under the ADVERSE REACTIONS section.

Post-Market Adverse Drug Reactions

These events were reported during post-marketing surveillance. Estimates of frequency cannot

be made since such events are reported voluntarily from a population of unknown size. Due to

the uncontrolled nature of spontaneous reports, a clear causal relationship to lansoprazole cannot

be established.

Body as a Whole: hypersensitivity reactions, including anaphylaxis;

Digestive System: colitis, hepatotoxicity, pancreatitis, vomiting;

Hemic and Lymphatic

System:

agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia,

neutropenia, pancytopenia, thrombocytopenia, and thrombotic

thrombocytopenic purpura;

Metabolism and

Nutritional Disorders:

Hypomagnesemia;

Musculoskeletal

System:

myositis, osteoporosis and osteoporosis-related fractures;

Skin and Appendages: severe dermatologic reactions including

cutaneous lupus erythematosus, erythema multiforme, Stevens-Johnson

syndrome, toxic epidermal necrolysis (some fatal);

Special Senses: speech disorder;

Urogenital System: interstitial nephritis (with possible progression to renal failure), urinary

retention.

In an estimated exposure of 240 million patients worldwide (in both postmarketing surveillance

and the clinical trials), the most commonly reported ophthalmic adverse events are amblyopia

(13) and vision blurred (67) according to the MedDRA terminology. All the 13 cases of

amblyopia had the reported term/verbatim "blurred or smeary vision". Only 2 of these 13 reports

were considered serious, and both are foreign-sourced reports with very little information

provided. Among the 67 reports with the “vision blurred,” 10 were considered serious and might

be related to optic neuritis/neuropathy, whether or not believed related to the drug. In 2 of these

10 cases, 1 of the examining ophthalmologists proposed a diagnosis of anterior ischemic optic

neuropathy (AION). Eight out of the 10 cases were foreign-sourced. Only 2 US-sourced serious

cases involved the report of blurred vision. Both were consumer reports without any detailed

information. No physician assessed any causality in either case.

Withdrawal of long term PPI therapy can lead to aggravation of acid related symptoms and may

result in Rebound Acid Hyper-secretion.


There have been post-marketing reports of subacute cutaneous lupus erythematosus (SCLE) (See

WARNINGS AND PRECAUTIONS, Immune).

There have been post-marketing reports of fundic gland polyps (FGPs) (see WARNINGS AND

PRECAUTIONS, Gastrointestinal).

DRUG INTERACTIONS

Overview

Lansoprazole is metabolized through the cytochrome P450 system, specifically through CYP3A

and CYP2C19. Studies have shown that lansoprazole does not have clinically significant

interactions with other drugs metabolized by the cytochrome P450 system such as warfarin,

antipyrine, indomethacin, acetylsalicylic acid, ibuprofen, phenytoin, prednisone, diazepam,

clarithromycin, propranolol, amoxicillin or terfenadine in healthy subjects. These compounds are

metabolized through various cytochrome P450 isozymes including CYP1A2, CYP2C9,

CYP2C19, CYP2D6, and CYP3A.

Drugs that Inhibit or Induce CYP2C19 Inhibitors of CYP2C19 such as fluvoxamine would likely increase the systemic exposure to

lansoprazole. Inducers of CYP2C19 may decrease the systemic exposure to lansoprazole.

Drugs with pH Dependent Absorption Pharmacokinetics Lansoprazole causes a profound and long lasting inhibition of gastric acid secretion; therefore,

lansoprazole may interfere with the absorption of drugs where gastric pH is an important

determinant of bioavailability (e.g., ketoconazole, ampicillin esters, iron salts, digoxin).

Drug-Drug Interactions

Table 10. Established or Potential Drug-Drug Interactions with Lansoprazole Concomitant

Drug Name Ref Effect Clinical Comment

Antiretroviral

Drugs

C

↓ rilpivirine,

atazanavir,

nelfinavir

↑saquinavir

Rilpivirine

Co-administration is contraindicated due to significant decreases in

rilpivirine exposure and loss of therapeutic effect (see

CONTRAINDICATIONS).

Atazanavir

Co-administration of lansoprazole with atazanavir is not recommended.

Concomitant administration of omeprazole (20 or 40 mg once daily)

substantially reduced plasma Cmax and AUC of atazanavir in healthy

volunteers administered atazanavir or atazanavir/ritonavir. (see

Atazanavir Product Monograph).

Nelfinavir

Co-administration of lansoprazole with nelfinavir is not recommended.

Concomitant administration of omeprazole (40 mg daily) with nelfinavir

(1250 mg twice daily) markedly reduced the AUC and Cmax for nelfinavir

(by 36% and 37%, respectively) and its active metabolite M8 (by 92%

and 89%, respectively). (see Nelfinavir Product Monograph).


Concomitant


Saquinavir

Co-administration of saquinavir requires caution and monitoring, along

with potential dose reduction of saquinavir, due to increased saquinavir

exposure and thus the risk of saquinavir-related toxicities. (see the Saquinavir Product Monograph).

Concomitant administration of omeprazole (40 mg daily) with

saquinavir/ritonavir (1000/100 mg twice daily) increased saquinavir AUC

by 82% and Cmax by 75%.

Clopidogrel

CT

- Concomitant administration of lansoprazole and clopidogrel in healthy

subjects had no clinically important effect on exposure to the active

metabolite of clopidogrel or clopidogrel-induced platelet inhibition. No

dose adjustment of clopidogrel is necessary when administered with an

approved dose of lansoprazole. CYP450 Methotrexate

C,

CT

- Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs

and methotrexate (primarily at high dose) may elevate and prolong serum

levels of methotrexate and/or its metabolite hydroxymethotrexate,

possibly leading to methotrexate toxicities. However, no formal drug

interaction studies of high dose methotrexate with PPIs have been

conducted.

In an open-label, single-arm, eight day, pharmacokinetic study of 28 adult

rheumatoid arthritis patients (who required the chronic use of 7.5 to 15

mg of methotrexate given weekly), administration of 7 days of naproxen

500 mg twice daily and lansoprazole 30 mg daily had no effect on the

pharmacokinetics of methrotrexate and 7-hydroxymethotrexate. While

this study was not designed to assess the safety of this combination of

drugs, no major adverse reactions were noted. However, this study was

conducted with low doses of methotrexate. A drug interaction study with

high doses of methotrexate has not been conducted. Sucralfate

CT

Lansoprazole:

AUC ↓, Cmax ↓

Proton pump inhibitors should be taken at least 30 minutes prior to

sucralfate. In clinical trials, antacids were administered with lansoprazole

and there was no evidence of a change in the efficacy of lansoprazole (see

ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics,

Absorption, Absorption with Antacids). Tacrolimus

C

Increased

whole blood

levels

Concomitant administration of lansoprazole and tacrolimus may increase

whole blood levels of tacrolimus, especially in transplant patients who are

intermediate or poor metabolizers of CYP2C19. Theophylline

(CYP1A2,

CYP3A)

CT

10% increase

in

theophylline

clearance

Minor increase of theophylline clearance is unlikely to be of clinical

concern.

Individual patients may require adjustment of their theophylline dosage

when lansoprazole is started or stopped to ensure clinically effective

blood levels.

Patient monitoring should be taken in coadministration of lansoprazole

with theophylline. Warfarin

C,

CT

↑ INR and PT

In a study of healthy subjects, neither the pharmacokinetics of warfarin

enantiomers nor prothrombin time were affected following co-

administration of single or multiple 60 mg doses of lansoprazole and

warfarin; however, there have been reports of increased INR and

prothrombin time in patients receiving proton pump inhibitors, including

lansoprazole, and warfarin concomitantly. Increases in INR and


Concomitant


prothrombin time may lead to abnormal bleeding and even death. Patients

treated with proton pump inhibitors and warfarin concomitantly may need

to be monitored for increases in INR and prothrombin time. Legend: C = Case Study; CT = Clinical Trial, T = Theoretical

Combination Therapy with Clarithromycin and/or Amoxicillin For more information on drug interactions for clarithromycin and amoxicillin, refer to their

respective Product Monographs, under DRUG INTERACTIONS.

Drug-Food Interactions

Food reduces the peak concentration and the extent of absorption by about 50% to 70%.

Therefore, it is recommended that lansoprazole delayed-release capsules be administered in the

morning prior to breakfast.

Drug-Laboratory Interactions

During treatment with antisecretory drugs, chromogranin A (CgA) increases due to decreased

gastric acidity. Increased Chromogranin A (CgA) level may interfere with investigations for

neuroendocrine tumours. To avoid this interference, lansoprazole delayed-release capsules

treatment should be stopped 14 days before CgA measurements (see ACTION AND CLINICAL

PHARMACOLOGY, Pharmacodynamics, Pharmacodynamic Properties).

DOSAGE AND ADMINISTRATION

Dosing Considerations

Duodenal Ulcer

Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy: Sandoz Lansoprazole/clarithromycin/amoxicillin



been established.

Gastric Ulcer Sandoz Lansoprazole (lansoprazole delayed-release capsules) is not indicated for maintenance

therapy in the treatment of patients with gastric ulcer.

Recommended Dose and Dosage Adjustment

Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the

condition being treated.

Duodenal Ulcer The recommended adult oral dose is 15 mg once daily before breakfast for 2 to 4 weeks (see

INDICATIONS AND CLINICAL USE).


A small percentage of patients who are H. pylori negative will experience a disease recurrence

and will require maintenance treatment with an antisecretory agent. Sandoz Lansoprazole 15 mg

once daily before breakfast may be used up to 1 year for the maintenance treatment of recurrent

duodenal ulcers.

Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy: Sandoz Lansoprazole/clarithromycin/amoxicillin

The recommended adult oral dose is 30 mg lansoprazole, 500 mg clarithromycin, and 1000 mg

amoxicillin, all given twice daily for 7, 10 or 14 days (see INDICATIONS AND CLINICAL

USE). Daily doses should be taken before meals.

(FOR ADDITIONAL INFORMATION ON TRIPLE THERAPY FOR THE

TREATMENT OF H. PYLORI INFECTION AND ACTIVE DUODENAL ULCER

RECURRENCE, REFER TO THE HP-PAC PRODUCT MONOGRAPH.)

Gastric Ulcer The recommended adult oral dose is 15 mg once daily before breakfast for 4 to 8 weeks.

No dosage adjustment is necessary in patients with renal impairment. No dosage adjustment is

necessary in the initial Sandoz Lansoprazole dosing regimen for older patients and for patients

with mild to moderate hepatic impairment. Dosing recommendations described in the labelling

should be adhered to for older patients and patients with hepatic impairment.

NSAID-Associated Gastric Ulcer The issue of whether or not eradication of H. pylori in patients with NSAID-associated ulcers

might have beneficial effects remains unresolved (Chan et al, 2001).

Healing of NSAID-Associated Gastric Ulcer

The recommended adult oral dose is 15 to 30 mg once daily before breakfast for up to 8 weeks.

A trend for higher healing rates (4% and 12%, two studies) was observed with the 30 mg dose, as

compared to the 15 mg dose (see CLINICAL TRIALS).

Reduction of Risk of NSAID-Associated Gastric Ulcer

The recommended adult oral dose is 15 mg once daily before breakfast for up to 12 weeks (see

CLINICAL TRIALS).

Reflux Esophagitis or Poorly Responsive Reflux Esophagitis Including Patients with

Barrett’s Esophagus

The recommended adult oral dose is 30 mg once daily before breakfast for 4 to 8 weeks (see

INDICATIONS AND CLINICAL USE).

Maintenance Treatment of Healed Reflux Esophagitis For the long-term management of patients with healed reflux esophagitis, 15 mg lansoprazole

given once daily before breakfast has been found to be effective in controlled clinical trials of

12 months (see CLINICAL TRIALS).


The recommended adult oral dose of Sandoz Lansoprazole for maintenance treatment of patients

with healed reflux esophagitis is 15 mg once daily before breakfast (see INDICATIONS AND

CLINICAL USE).

Treatment and Maintenance of Pathological Hypersecretory Conditions Including

Zollinger-Ellison Syndrome

The dosage of Sandoz Lansoprazole in patients with pathologic hypersecretory conditions varies

with the individual patient. The recommended adult oral starting dose is 60 mg once a day.

Doses should be adjusted to individual patient needs and should continue for as long as clinically

indicated. Dosages up to 90 mg twice daily have been administered. Daily dosages of greater

than 120 mg should be administered in divided doses. Some patients with Zollinger-Ellison

Syndrome have been treated continuously with lansoprazole for more than 4 years (see

CLINICAL TRIALS).

Gastroesophageal Reflux Disease (GERD)

Short-Term Treatment of Symptomatic GERD

The recommended adult oral dose for the treatment of heartburn and other symptoms associated

with GERD is 15 mg once daily before breakfast for up to 8 weeks. If significant symptom relief

is not obtained within 4 to 8 weeks, further investigation is recommended.

Pediatric GERD (erosive and non-erosive esophagitis)

In clinical studies, lansoprazole was not administered beyond 12 weeks in 6 to 11 year olds. It is

not known if lansoprazole is safe and effective if used longer than the recommended duration.

Do not exceed the recommended dose and duration of use in children as outlined below.

Children 6 to 11 years of age

The recommended pediatric oral dose for children 6 to 11 years of age is 15 mg (≤ 30 kg) and

30 mg (>30 kg) once daily for up to 12 weeks.

Children 12 to 17 years of age

For adolescents of 12 to 17 years, the same approved regimen for adults can be used.

Patients with Hepatic Impairment

The daily dose of Sandoz Lansoprazole should not exceed 30 mg (see WARNINGS AND

PRECAUTIONS).

Patients with Renal Impairment

No dosage modification of Sandoz Lansoprazole is necessary (see WARNINGS AND

PRECAUTIONS).

Elderly Patients

The daily dose should not exceed 30 mg (see WARNINGS AND PRECAUTIONS).


Missed Dose

Patients should be instructed that if a dose of this medication has been missed, it should be taken

as soon as possible. However, if the next scheduled dose is due, the patient should not take the

missed dose, and should be instructed to take the next dose on time. Patients should be instructed

not to take 2 doses at one time to make up for a missed dose.

Administration

Sandoz Lansoprazole should be taken daily before breakfast. Where the product may be used

twice daily, it should be taken prior to breakfast and another meal. Sandoz Lansoprazole capsules

SHOULD NOT BE CRUSHED, CHEWED, BROKEN OR CUT.

Concomitant Antacid Use

Simultaneous administration of Sandoz Lansoprazole with aluminum and magnesium hydroxide

or magaldrate results in lower peak plasma levels, but does not significantly reduce

bioavailability. Antacids may be used concomitantly if required. If sucralfate is to be given

concomitantly, Sandoz Lansoprazole should be administered at least 30 minutes prior to

sucralfate (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Absorption,

Absorption with Antacids). In clinical trials, antacids were administered concomitantly with

lansoprazole delayed-release capsules; this did not interfere with its effect.

OVERDOSAGE

For management of a suspected drug overdose, contact your regional Poison Control Centre.

As in all cases where overdosing is suspected, treatment should be supportive and symptomatic.

Any unabsorbed material should be removed from the gastrointestinal tract, and the patient

should be carefully monitored. Lansoprazole is not removed from the circulation by

hemodialysis. In one reported case of overdose, the patient consumed 600 mg of lansoprazole

with no adverse reaction.

Oral doses up to 5000 mg/kg in rats (approximately 1300 times the recommended human dose

based on body surface area) and mice (about 675.7 times the recommended human dose based on

body surface area) did not produce deaths or any clinical signs.

ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

Lansoprazole delayed-release capsules inhibit the gastric H+, K+-ATPase (the proton pump)

which catalyzes the exchange of H+ and K+. They are effective in the inhibition of both basal

acid secretion and stimulated acid secretion.

Pharmacodynamics

In healthy subjects, single and multiple doses of lansoprazole delayed-release capsules (15 mg to

60 mg) have been shown to decrease significantly basal gastric acid output and to increase


significantly mean gastric pH and percent of time at pH >3 and 4. These doses have also been

shown to reduce significantly meal-stimulated gastric acid output and gastric secretion volume.

Single or multiple doses of lansoprazole delayed-release capsules (10 mg to 60 mg) reduced

pentagastrin-stimulated acid output. In addition, lansoprazole delayed-release capsules have been

demonstrated to reduce significantly basal and pentagastrin-stimulated gastric acid secretion

among Duodenal Ulcer and hypersecretory patients, and basal gastric acid secretion among

patients with Gastric Ulcer disease.

A dose-response effect was analyzed by considering the results from clinical pharmacology

studies that evaluated more than one dose of lansoprazole delayed-release capsules. The results

indicated that, in general, as the dose was increased from 7.5 mg to 30 mg, there was a decrease

in mean gastric acid secretion and an increase in the average time spent at higher pH values

(pH >4).

The results of pharmacodynamic studies with lansoprazole delayed-release capsules in normal

subjects suggest that doses of 7.5 to 10 mg are substantially less effective in inhibiting gastric

acid secretion than doses of 15 mg or greater. In view of these results, the doses of lansoprazole

delayed-release capsules evaluated in the principal clinical trials ranged from 15 mg to 60 mg

daily.

Pharmacodynamic Properties

During treatment with antisecretory medicinal products, serum gastrin increases in response to

the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased

CgA level may interfere with investigations for neuroendocrine tumours.

Available published evidence suggests that proton pump inhibitors should be discontinued 14

days prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated

following PPI treatment to return to reference range (see WARNINGS AND PRECAUTIONS,

Interference with Laboratory Tests).

Eradication of Helicobacter pylori Helicobacter pylori is considered to be a major factor in the etiology of duodenal ulcer disease.

The presence of H. pylori may damage the mucosal integrity due to the production of enzymes

(catalase, lipases, phospholipases, proteases, and urease), adhesins and toxins; the inflammatory

response generated in this manner contributes to mucosal damage.

The concomitant administration of an antimicrobial(s) and an antisecretory agent such as

lansoprazole, improves the eradication of H. pylori as compared to individual drug

administration. The higher pH resulting from antisecretory treatment, optimizes the environment

for the pharmacologic action of the antimicrobial agent(s) against H. pylori.

Pharmacokinetics

Lansoprazole delayed-release capsules contain an enteric-coated granule formulation of

lansoprazole to ensure that absorption of lansoprazole begins only after the granules leave the

stomach (lansoprazole is acid-labile). Peak plasma concentrations of lansoprazole (Cmax) and the

area under the plasma concentration curve (AUC) of lansoprazole are approximately


proportional in doses from 15 mg to 60 mg after single-oral administration. Lansoprazole

pharmacokinetics are unaltered by multiple dosing and the drug does not accumulate.

Lansoprazole delayed-release capsules are highly bioavailable when administered orally. In a

definitive absolute bioavailability study, the absolute bioavailability was shown to be 86% for a

15 mg capsule and 80% for a 30-mg capsule. First pass effect is apparently minimal.

Table 11 summarizes the pharmacokinetic parameters (Tmax, T½, AUC and Cmax) of lansoprazole

delayed-release capsules in healthy subjects. For a summary of pharmacokinetic, metabolism and

excretion data in animals, see DETAILED PHARMACOLOGY, Animal.

Table 11. Pharmacokinetic Parameters of Lansoprazole Delayed-Release Capsules Pooled

Across Phase I Studies Parameter Tmax (h) T½ (h) AUC * (ng•h/mL) Cmax * (ng/mL)

Mean 1.68 1.53 2133 824

Median 1.50 1.24 1644 770

SD 0.80 1.01 1797 419

% CV 47.71 65.92 84.28 50.81

Min 0.50 0.39 213 27

Max 6.00 8.50 14203 2440

N† 345 285 513 515 * Normalized to a 30 mg dose † Number of dosages associated with a parameter

Absorption: The absorption of lansoprazole is rapid, with mean peak plasma levels of

lansoprazole occurring at approximately 1.7 hours. Peak plasma concentrations of lansoprazole

(Cmax) and the area under the plasma concentration curve (AUC) are approximately proportional

to dose throughout the range that has been studied (up to 60 mg).

Absorption with Food

Food reduces the peak concentration and the extent of absorption by about 50% to 70%.

Moreover, the results of a pharmacokinetic study that compared the bioavailability of

lansoprazole following a.m. dosing (fasting) versus p.m. dosing (3 hours after a meal) indicated

that both Cmax and AUC values were increased by approximately 2-fold or more with a.m.

dosing. Therefore, it is recommended that lansoprazole delayed-release capsules be administered

in the morning prior to breakfast.

Absorption with Antacids

Simultaneous administration of lansoprazole delayed-release capsules with aluminum and

magnesium hydroxide or magaldrate resulted in lower peak serum levels, but did not

significantly reduce the bioavailability of lansoprazole.

In a single-dose crossover study when 30 mg of lansoprazole was administered concomitantly

with 1 gram of sucralfate in healthy volunteers, absorption of lansoprazole was delayed and its

bioavailability was reduced. The value of lansoprazole AUC was reduced by 17% and that for

Cmax was reduced by 21%.


In a similar study when 30 mg of lansoprazole was administered concomitantly with 2 grams of

sucralfate, lansoprazole AUC and Cmax were reduced by 32% and 55%, respectively. When

lansoprazole dosing occurred 30 minutes prior to sucralfate administration, Cmax was reduced by

only 28% and there was no statistically significant difference in lansoprazole AUC. Therefore,

lansoprazole may be given concomitantly with antacids but should be administered at least

30 minutes prior to sucralfate.

Distribution: The apparent volume of distribution of lansoprazole is approximately 15.7 (±

1.9) L, distributing mainly in extracellular fluid. Lansoprazole is 97% bound to plasma proteins.

The mean total body clearance (CL) of lansoprazole was calculated at 31 ± 8 L/h, and the

volume of distribution (Vss) was calculated to be 29 (± 4) L.

Metabolism: Lansoprazole is extensively metabolized in the liver. Two metabolites have been

identified in measurable quantities in plasma; the hydroxylated sulfinyl and the sulfone

derivatives of lansoprazole. These metabolites have very little or no antisecretory activity.

Lansoprazole is thought to be transformed into 2 active species that inhibit acid secretion by

blocking the proton pump (H+, K+)-ATPase enzyme system at the secretory surface of the gastric

parietal cell. The 2 active species are not present in the systemic circulation. The plasma

elimination half-life of lansoprazole is less than 2 hours while the acid inhibitory effect lasts

more than 24 hours. Therefore, the plasma elimination half-life of lansoprazole does not reflect

its duration of suppression of gastric acid secretion.

Excretion: Following single dose oral administration of lansoprazole, virtually no unchanged

lansoprazole was excreted in the urine. After a 30 mg single oral dose of 14C-lansoprazole,

approximately one-third of the dose was excreted in the urine and approximately two-thirds were

recovered in the feces. This implies a significant biliary excretion of the metabolites of

lansoprazole.

Following a 30 mg single intravenous dose of lansoprazole, the mean clearance was

11.1 (± 3.8) L/h.

Special Populations and Conditions

Pediatrics (1 to 17 years of age): The pharmacokinetics of lansoprazole were studied in

pediatric patients with Gastroesophageal Reflux Disease (GERD) aged 1 to 11 years, with

lansoprazole doses of 15 mg once daily for subjects weighing ≤ 30 kg and 30 mg once daily for

subjects weighing > 30 kg. The pharmacokinetics were also studied in adolescents aged

12 to 17 years with GERD following 15 mg or 30 mg once daily of lansoprazole.

Pharmacokinetic parameters for lansoprazole following 15 or 30 mg once daily doses of

lansoprazole to children aged 1 to 11 years and adolescents aged 12 to 17 years, as well as those

observed from healthy adult subjects, are summarized in Table 12.

Table 12. Mean ± SD Pharmacokinetic Parameters of Lansoprazole in Children,

Adolescents and Adults Pharmacokinetic

Parameter

Children Aged 1 to 11 yrs

(M97-808)

Adolescents Aged 12 to 17 yrs

(M97-640)

Healthy Adults

Aged ≥18 yrs

15 mg * 30 mg * 15 mg 30 mg 30 mg †


Pharmacokinetic

Parameter

Children Aged 1 to 11 yrs

(M97-808)

Adolescents Aged 12 to 17 yrs

(M97-640)

Healthy Adults

Aged ≥18 yrs

Tmax(h) 1.5 ± 0.7 1.7 ± 0.7 1.6 ± 0.7 1.7 ± 0.7 1.7 ± 0.8

Cmax (ng/mL) 790.9 ± 435.4 898.5 ± 437.7 414.8 ± 215.5 1005 ± 604.9 824 ± 419

Cmax/D(ng/mL/mg) - - 27.7 ± 14.4 33.5 ± 20.2 27.5 ± 14.0

AUC (ng•h/mL) 1707 ± 1689 1883 ± 1159 1017 ± 1737 2490 ± 2522 2133 ± 1797

AUC/D

(ng•h/mL/mg) - - 67.8 ± 115.8 83.0 ± 84.1 71.1 ± 59.9

t1/2 (h) ‡ 0.68 ± 0.21 0.71 ± 0.22 0.84 ± 0.26 0.95 ± 0.31 1.19 ± 0.52 * Subjects with a body weight of ≤30 kg were administered a 15-mg dose; subjects with a body weight of

>30 kg were administered a 30-mg dose. † Data obtained from healthy adult subjects normalized to a 30 mg dose. ‡ Harmonic mean ± Pseudo Standard Deviation.

In general, the pharmacokinetics of lansoprazole in children and adolescents (aged 1 to 17 years)

with GERD were similar to those observed in healthy adult subjects.

Children 1 to 11 years old weighing ≤ 30 kg received a 15 mg dose and children weighing

>30 kg received a 30 mg dose. When normalized for body weight, the mean lansoprazole dose

was similar for the two dosing groups (0.82 mg/kg for 15 mg dose group and 0.74 mg/kg for

30 mg dose group). The Cmax and AUC values were therefore similar for both the 15 mg and

30 mg dose groups.

In adolescent subjects aged 12 to 17 years, a nearly proportional increase in plasma exposure was

observed between 15 mg and 30 mg once daily dosing groups. Plasma exposure of lansoprazole

was not affected by body weight or age; and nearly dose-proportional increases in plasma

exposure were observed between the two dose groups in the study. The results of the study in

adolescents demonstrated that the pharmacokinetics of lansoprazole in this group is similar to

that previously reported in healthy adult subjects.

Geriatrics: The results from the studies that evaluated the pharmacokinetics of lansoprazole

following oral administration in an older population revealed that in comparison with younger

subjects, older subjects exhibited significantly larger AUCs and longer t½s. Lansoprazole did not

accumulate in the older subjects upon multiple dosing since the longest mean t½ in the studies

was 2.9 hours, and lansoprazole is dosed once daily. Cmax in the elderly was comparable to that

found in adult subjects.

Gender: The pharmacokinetic data of intravenous lansoprazole in females is limited; however,

in a study with oral lansoprazole comparing 12 male and 6 female subjects, no gender

differences were found in pharmacokinetics or intragastric pH results (see WARNINGS AND

PRECAUTIONS, Use in Women).

Race: The pooled pharmacokinetic parameters of oral administered lansoprazole from twelve

U.S. Phase I studies (N=513) were compared to the mean pharmacokinetic parameters from two

Asian studies (N=20). The mean AUCs of lansoprazole in Asian subjects are approximately

twice that seen in pooled U.S. data, however, the inter-individual variability is high. The Cmax

values are comparable.


Hepatic Impairment: As would be expected with a drug that is primarily metabolized by the

liver, in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) chronic

hepatic disease, the plasma half-life of the drug after oral administration increased to 5.2 hours

compared to the 1.5 hours half-life in healthy subjects. An increase in AUC of 3.4 fold was

observed in patients with hepatic impairment versus healthy subjects (7096 versus

2645 ng•h/mL) which was due to slower elimination of lansoprazole; however, Cmax was not

significantly affected. Dose reduction in patients with severe hepatic disease should be

considered.

Renal Impairment: In patients with mild (Clcr 40 to 80 mL/min), moderate (Clcr 20 to

40 mL/min) and severe (Clcr


Sandoz Lansoprazole is available as 30 mg pink cap-black body capsules imprinted with “30” in

white ink on the body and containing white to off white pellets. The capsules are available in

bottles of 100 and 500.


PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION

Drug Substance

Proper Name: Lansoprazole

Chemical Name: 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-

benzimidazole

Molecular Formula: C16H14F3N3O2S

Molecular Mass: 369.36 g/mol

Structural Formula:

Physicochemical Properties:

Lansoprazole is a white to brownish-white powder. Lansoprazole is freely soluble

in dimethylformamide; slightly soluble in methanol; sparingly soluble in ethanol;

slightly soluble in ethyl acetate, dichloromethane and acetonitrile; very slightly

soluble in ether; and practically insoluble in water and hexane.

pKa Values: pKa1 = 8.84

pKa2 = 4.15

pKa3 = 1.33


CLINICAL TRIALS

Comparative Bioavailability Studies

A blinded, randomized, single dose, two-way cross-over comparative bioavailability study of

Sandoz Lansoprazole (lansoprazole) 30 mg delayed-release capsules (Sandoz Canada Inc.)

versus PREVACID® (lansoprazole) 30 mg delayed-release capsules (Takeda Pharmaceuticals

America Inc.) in 60 healthy adult mate volunteers was conducted under fasting conditions.

Bioavailability data were measured and the results from 54 subjects are summarized in the

following table.

SUMMARY TABLE OF THE COMPARATIVE BIOAVAILABILITY DATA UNDER FASTING

CONDITIONS

Lansoprazole

(1 X 30 mg)

From measured data

Geometric Mean

Arithmetic Mean (CV %)

Parameter Test* Reference†

Ratio of

Geometric

Means (%)

90 % Confidence

Interval (%)

AUCT (ng.h / mL)

3419.827

4520.886 (80.1)

3597.222

4606.701 (76.2) 95.1 87.98 -102.74

AUCI (ng.h / mL)

3483.413

4643.675 (82.5)

3670.424

4745.526 (78.5) 94.9 87.93 – 102.46

Cmax (ng / mL)

1119.929

1214.787 (38.1)

1155.172

1225.902 (33.1) 97.0 88.58 -106.20

Tmax§ (h) 1.750 (0.833 - 3.000) 1.625 (0.833 – 4.500)

T½€ (h) 2.112 (68.7) 2.180 (73.4) * Sandoz Lansoprazole (lansoprazole) 30 mg delayed-release capsules (Sandoz Canada Inc.) † PREVACID ® (lansoprazole) 30 mg delayed-release capsules (Takeda Pharmaceuticals America Inc.) were

purchased in Canada. § Expressed as the median (range) only € Expressed as the arithmetic mean (CV%) only


A blinded, randomized, single dose, two-way cross-over comparative bioavailability study of

Sandoz Lansoprazole (lansoprazole) 30 mg delayed-release capsules (Sandoz Canada Inc.) versus

PREVACID® (lansoprazole) 30 mg delayed-release capsules (Takeda Pharmaceuticals America

Inc.) in 130 healthy adult male volunteers was conducted under fed conditions. Bioavailability

data were measured and the results from 124 subjects are summarized in the following table.

SUMMARY TABLE OF THE COMPARATIVE BIOAVAILABILITY DATA

UNDER FED CONDITIONS

Lansoprazole

(1 X 30 mg)

From measured data

Geometric Mean

Arithmetic Mean (CV %)

Parameter Test* Reference†

Ratio of

Geometric

Means (%)

90 % Confidence

Interval (%)

AUCT (ng.h / mL)

1617.533

2496.378 (101.1)

1723.605

2602.731 (106.4) 93.8 85.24 – 103.26

AUCI (ng.h / mL)

1711.003

2650.268 (104.0)

1828.964

2777.700 (110.7) 93.8 85.37 – 102.96

Cmax (ng / mL)

423.698

540.997 (65.1)

419.276

530.789 (68.7) 101.0 91.01 – 112.19

Tmax§ (h) 4.000 (2.000-8.000) 3.667 (1.667-6.000)

T½€ (h) 2.106 (77.4) 2.231 (79.3) * Sandoz Lansoprazole (lansoprazole) 30 mg delayed-release capsules (Sandoz Canada Inc.). † PREVACID® (lansoprazole) 30 mg delayed-release capsules (Takeda Pharmaceuticals America Inc.) were

purchased in Canada. § Expressed as the median (range) only € Expressed as the arithmetic mean (CV%) only


Duodenal Ulcer In a U.S. multicenter, double-blind, placebo-controlled, dose-response (15, 30, and 60 mg of

lansoprazole delayed-release capsules once daily) study of 284 patients with endoscopically

documented duodenal ulcer, the percentage of patients healed after 2 and 4 weeks was

significantly higher with all doses of lansoprazole delayed-release capsules than with placebo

(Table 13). There was no evidence of a greater or earlier response with the two higher doses

compared with lansoprazole delayed-release 15 mg. Based on this study and the second study

described below, the recommended dose of lansoprazole delayed-release in duodenal ulcer is

15 mg/day.

Table 13. Duodenal Ulcer Healing Rates Week

Lansoprazole

15 mg once daily

(N = 68)

Lansoprazole

30 mg once daily

(N = 74)

Lansoprazole

60 mg once daily

(N = 70)

Placebo

(N = 72)

2 42.4%* 35.6%* 39.1%* 11.3%

4 89.4%* 91.7%* 89.9%* 46.1%

* (p ≤ 0.001) versus placebo.

Lansoprazole delayed-release capsules 15 mg were significantly more effective than placebo in

relieving day and nighttime abdominal pain and in decreasing the amount of antacid taken per

day.

In a second U.S. multicenter study, also double-blind, placebo-, dose-comparison (15 and 30 mg

lansoprazole delayed-release capsules once daily), and including a comparison with ranitidine, in

280 patients with endoscopically documented duodenal ulcer, the percentage of patients healed

after 4 weeks was significantly higher with both doses of lansoprazole delayed-release than with

placebo (Table 14). There was no evidence of a greater or earlier response with the higher dose

of lansoprazole delayed-release. The 15 mg dose of lansoprazole delayed-release was superior to

ranitidine at 4 weeks. No significant difference was seen between treatment groups at 2 weeks.

In addition, no difference between lansoprazole delayed-release and ranitidine was noted at

4 weeks.

Table 14. Duodenal Ulcer Healing Rates Week

Lansoprazole

15 mg once daily

(N = 80)

Lansoprazole

30 mg once daily

(N = 77)

Ranitidine

300 mg at bedtime

(N = 82)

Placebo

(N = 41)

2 35.0% 44.2% 30.5% 34.2%

4 92.3%* 80.3%† 70.5%† 47.5%

* (p ≤ 0.05) versus placebo and ranitidine.

† (p ≤ 0.05) versus placebo.

Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Randomized, double-blind clinical studies in patients with H. pylori and duodenal ulcer disease

(defined as an active ulcer or history of an ulcer within 1 year) evaluated the efficacy of

lansoprazole delayed-release capsules in combination with amoxicillin capsules and

clarithromycin tablets as triple 14-day therapy, or in combination with amoxicillin as dual 14-day

therapy for the eradication of H. pylori. Based on the results of these studies, the safety and

efficacy of two different eradication regimens were established:


Triple therapy: lansoprazole delayed-release capsules 30 mg twice daily/clarithromycin 500 mg

twice daily / amoxicillin 1000 mg twice daily

Dual therapy: lansoprazole delayed-release capsules 30 mg three times daily / amoxicillin

1000 mg three times daily

All treatments were for 14 days. H pylori eradication was defined as two negative tests (culture

and histology) at 4 to 6 weeks following the end of treatment.

Triple therapy was shown to be more effective than all possible dual therapy combinations

(Table 15). Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer

recurrence.

A randomized, double-blind clinical study performed in the

PRODUCT MONOGRAPH - Sandoz...Lansoprazole, in combination with clarithromycin plus amoxicillin as triple therapy, is indicated for the treatment of patients with H. pylori infection

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